This invention relates to interferon inducer, a process for producing the same and pharmaceutical composition containing the same.
Interferon, hereinafter referred to as IF is a substance capable of acting upon animal or human cells to inhibit the growth of a virus and is a type of protein liberated from the cell in response to viral infection. The activity of IF is specific with respect to an animal species and non-specific with respect to a viral species and may vary, with differing conditions used for its induction. It is also known that the growth of certain animal type viruses may significantly be inhibited by IF under certain conditions.
A substance capable of acting upon animal or humans cells to induce IF is designated as an IF inducer. Thus, an IF inducer is of potential interest in the prevention and treatment of various human and animal diseases caused by viral infection. However, various known IF inducers have never been used in practice for such a purpose because of certain defects. Thus, for example, U.S. Pat. Nos. 3,583,893 (1971) discloses the production of a double-stranded ribonucleic acid as an IF inducer originating from a microorganism and describes in its prior art statement that many substances including bacteria, viruses, polysaccharides, mitogenic agents, endotoxin and the like stimulate interferon formation but none is of interest for routine use because of their inter alia toxicity, antigenicity and infectiousness. It has thus been believed that IF inducers isolated from microorganisms are in general disadvantageous for therapeutic use because of their high toxicity.
Examples of known mitogenic agents isolated from the tissues of higher plants include phytohemagglutinin (PHA) [Wheelock, Science, 149:301 (1965) and J. Biol. Chem. 212, 607-615 (1955)], pokeweed mitogen [Friedman et al, Proc. Soc. Exp. Med., 125:90 (1967) and J. Exp. Med., 124:859-972 (1966)] and concanavallin A [Willen et al., Cell. Immunol., 6:110 (1973) and Methods of Carbohydrate Chem., vol. VI, 108-110 (1972)] respectively isolated from the tissues of kidney bean, pokeweed and horse bean by extracting with a saline or buffer solution, treating the extracted solution with an alcohol, followed by purification with column chromatography. Due to their extremely low IF-inducing activity, however, no successful attempt has been made to use these mitogenic agents for preventing and treating various diseases cause by viral infection.
Other IF inducers isolated from higher plants are also known. That is, Kojima et al [Japanese Patent Application as laid open to public inspection as Kokai Koho 32107/78] disclosed an IF inducer which is believed to be a kind of heteropolymeric saccharide containing as main constituents hexose (48%), protein (5%) and uronic acid (40%), and having a molecular weight of more than 100,000. This substance is isolated from the root of Angelica acutiloba Kitagawa (known in Japan as Toki) by extracting the root with hot water to give an extracted solution, subjecting the same to dialysis to give a residue, adding acetone to the residue to give a precipitate and freeze-drying the same. The extracted solution may, if desired, be made up to a suitable quantity by concentrating under reduced pressure or by using a Diaflo membrane (MW 10,000), followed by dialysis. Subsequently, Kojima and Tamamura [Japanese Patent Application laid open to public inspection as Kokai Koho 99313/78] disclosed an IF inducer having a molecular weight of more than 20,000 (mainly more than 60,000) and containing as main constituents a 1-3 bonded glucose (hexose: more than 90%). This IF inducer is produced by extracting the peeling of a mulberry e.g. Morus alba L or M. bombycis Koidzumi with hot water, adding an organic solvent to the extracted solution to give a precipitate, adding a small amount of water to the same, subjecting the mixture to dialysis to give a residue and freeze-drying the same. If desired, the solution after extraction or before dialysis may be made up to a suitable quantity either by concentrating under reduced pressure or by using a Diaflo membrane.
These two IF inducers isolated from the tissues of higher plants have high IF-inducing activity and low toxicity and may be obtained readily and cheaply. However, the cheap and abundant supply of the raw material may cease as a result of the continuous use of these plants over many years as the source of Sino-Japanese traditional drugs.